Yoo Hyun Um

Automated quantification of amyloid positron emission tomography: a comparison of PMOD and MIMneuro

ObjectiveThe aim of this study was to examine and compare two automated quantitative software tools (PMOD and MIMneuro) for the quantification of amyloid positron emission tomography (PET).MethodsA total of 30 subjects—15 Alzheimer’s disease (AD) patients and 15 cognitively normal age- and sex-matched controls—were enrolled. All subjects underwent structural volumetric magnetic resonance imaging (MRI) and amyloid PET scans with F-18 florbetaben. Regional standardized uptake value ratios (SUVRs) using the cerebellar cortex as a reference region were obtained using PMOD and MIMneuro.ResultsThe SUVRs using both PMOD and MIMneuro showed high discriminatory power between the AD patients and cognitively normal controls. While PMOD and MIMneuro yielded significantly different SUVRs in some brain regions, the two methods had good overall agreement.ConclusionMIMneuro provides comparable performance to PMOD without the need to acquire brain MRI. Therefore, MIMneuro might be suitable for clinical use to determine amyloid positivity.

Cerebral Vascular Burden on Hippocampal Subfields in First-onset Drug-naïve Subjects with Late-Onset Depression

BACKGROUND Although there is substantial evidence of associations between frontal-striatal circuits and cerebral vascular burden in late-onset depression (LOD), relationships between vascular burden and hippocampal subfields are not clear. The purpose of this study was to investigate relationships between cerebral vascular burden and hippocampal subfield volume in LOD patients. METHODS Fifty subjects with LOD and 50 group-matched healthy control subjects underwent magnetic resonance imaging scanning. Hippocampal subfields volumes were measured and compared between the groups. In addition, association patterns between white matter hyperintensity (WMH) volumes, clinical measures and hippocampal subfield volumes were investigated in the LOD group. RESULTS Subjects with LOD exhibited significant hippocampal volume reductions in the total hippocampus, cornu ammonis (CA) 1 and 3 and dentate gyrus (DG) areas compared with healthy subjects. Total WMH volume was negatively correlated with left total hippocampal volume and CA1 in the LOD group. In addition, depression severity was negatively associated with left and right CA3 volumes in the LOD group. LIMITATION Our findings of distinctive relationships between WMH and hippocampal subfields demonstrate a simple correlation, but do not prove causation CONCLUSION: This study is the first to elaborate distinctive association patterns between hippocampal subfield volumes and cerebral vascular burden in LOD. These structural changes in the hippocampal CA1, CA3 and DG areas might be at the core of the underlying neurobiological mechanisms of hippocampal dysfunction in LOD. However, longitudinal studies will be needed to identify the mechanisms of these structural changes.

Depression and Mortality in People with Type 2 Diabetes Mellitus, 2003 to 2013: A Nationwide Population-Based Cohort Study

Background Previous reports have demonstrated a bidirectional relationship between depression and diabetes mellitus (DM), accentuating a need for more intensive depression screening in DM patients. There is a relative paucity of data on the mortality of depressed DM patients in Korea. Methods Retrospective data from January 2003 to December 2013 were collected for adult type 2 diabetes mellitus (T2DM) patients older than 30 years using the National Health Information database maintained by the Korean National Health Insurance Service (NHIS). Demographic characteristics were analyzed with descriptive statistics, and the annual prevalence of depression was estimated. Mortality rates and hazard ratios for each age group (stratified into six age groups) of patients diagnosed with T2DM in 2003 were estimated using a Cox proportional hazard method, with the Kaplan-Meier cumulative survival curve showing the overall survival rates according to the T2DM status until the given year of 2013. Results The annual prevalence of depression was consistently higher in T2DM group from 2003 to 2013. The mortality hazard ratio was higher in the depressed in all age groups, and the risk was higher in male groups and in younger-aged groups. Conclusion Depression was significantly associated with a high mortality risk in T2DM patients; hence, a more systematic surveillance of T2DM patients to identify risk factors for depression might contribute significantly to reducing mortality risk in this group of patients.

Impact of Amyloid Burden on Regional Functional Synchronization in the Cognitively Normal Older Adults

Previous studies have shown aberrant functional connectivity in preclinical Alzheimer’s disease (AD). However, the effects of beta-amyloid (Aβ) retention on regional functional synchronization in cognitively normal older adults still remain unclear. The aim of this study was to explore the distinctive association pattern between Aβ retention and regional functional synchronization in cognitively normal older adults. Sixty-one older adults with normal cognition underwent functional magnetic resonance imaging and regional functional synchronizations were quantified using regional homogeneity (ReHo). Subjects were dichotomized using 18F-Florbetaben positron emission tomography imaging into subjects with (Aβ+; n = 30) and without (Aβ-; n = 31) Aβ burden. The Aβ+ group exhibited significantly higher ReHo in the fusiform gyrus and lower ReHo in the precuneus compared with the Aβ- group. We found significant negative correlations between global Aβ retention and ReHo in the precuneus and medial prefrontal cortex and positive correlations between global Aβ retention and ReHo in the bilateral lingual gyrus, left fusiform gyrus, and right middle temporal gyrus in the Aβ+ group. Our findings suggest that regional functional synchronization might have distinctive association patterns with Aβ retention in the cognitively normal older adults. These findings can enrich the functional characterization of early stages of disease progression in AD.

Sleep Problems as Predictors in Attention-Deficit Hyperactivity Disorder: Causal Mechanisms, Consequences and Treatment

Attention-deficit hyperactivity disorder (ADHD) is notorious for its debilitating consequences and early age of onset. The need for early diagnosis and intervention has frequently been underscored. Previous studies have attempted to clarify the bidirectional relationship between ADHD and sleep problems, proposing a potential role for sleep problems as early predictors of ADHD. Sleep deprivation, sleep-disordered breathing, and circadian rhythm disturbances have been extensively studied, yielding evidence with regard to their induction of ADHD-like symptoms. Genetic-phenotypic differences across individuals regarding the aforementioned sleep problems have been elucidated along with the possible use of these characteristics for early prediction of ADHD. The long-term consequences of sleep problems in individuals with ADHD include obesity, poor academic performance, and disrupted parent-child interactions. Early intervention has been proposed as an approach to preventing these debilitating outcomes of ADHD, with novel treatment approaches ranging from melatonin and light therapy to myofunctional therapy and adjustments of the time point at which school starts.

A Case Report of a 37-Year-Old Alzheimer's Disease Patient with Prominent Striatum Amyloid Retention

With recent advancement in amyloid imaging, diagnostic application of this new modality has become a great interest among researchers. New ligands, such as 18F- florbetaben, florbetapir and flutemetamol, have been discovered to overcome limitations of preexisting ligand Pittsburgh compound B. We report here a case of a 37-year-old male patient whose initial complaints comprised of gradual cognitive decline, apraxia, disorientation and sleep disturbances. 18F-Florbetaben amyloid imaging of the patient showed diffuse amyloid retention with prominent striatal uptake. This finding supports the clinical utility of amyloid imaging in diagnostic process of early-onset AD. Moreover, striatal dominant uptake pattern demonstrated in this patient include some meaningful clinical implications that warrant special attention among clinicians.

A Longitudinal Follow-Up Study on Multiple Sleep Latency Test and Body Mass Index of Patients With Narcolepsy Type 1 in Korea

STUDY OBJECTIVES Narcolepsy is a chronic disorder with numerous adverse long-term consequences including increased obesity, high mortality rates, and decreased quality of life. With emerging attention to the long-term course of the disorder and importance of accurate diagnosis, the diagnostic stability of the Multiple Sleep Latency Test (MSLT)-the mostly frequently used test to identify narcolepsy-is often challenged. METHODS In this study, we compared the baseline and follow-up demographic characteristics and body mass index (BMI) of patients with narcolepsy type 1. Moreover, MSLT results from repeated tests conducted on 48 patients with narcolepsy type 1 were compared, with mean follow-up of approximately 10 years. RESULTS BMI from the baseline to the follow-up visit was significantly increased in the participants. There were no significantly different parameter changes in MSLT results. CONCLUSIONS MSLT has good test-retest validity in patients with narcolepsy type 1. Close surveillance for the detection and management of obesity is warranted in clinical settings.

Limbic Encephalitis Manifesting as Selective Amnesia and Seizure-like Activity: A Case Report

Limbic encephalitis (LE) is characterized by short-term memory loss, disorientation, agitation, seizures, and histopathological evidence of medial temporal lobe inflammation. Leucine-rich, glioma inactivated 1 (LGI-1) is an auto-antigen associated with LE. We report a 37-year-old male patient with LGI-1-related LE who presented with recurrent episodes of selective amnesia, seizure-like activity, confusion, and personality change. His symptoms were significantly improved with steroid therapy. Thorough differential diagnosis with consideration for autoimmune encephalitis should be in patients with presentation of symptoms, such as memory impairment, personality change and seizure-like activity, especially when other neurological diagnoses are excluded.

PREDICTION OF TREATMENT RESPONSE TO DONEPEZIL USING AUTOMATED HIPPOCAMPAL SUBFIELD VOLUMES SEGMENTATION IN PATIENTS WITH MILD ALZHEIMER’S DISEASE

atrophy rates using a linear mixed-effects model and from the model calculated sample sizes per arm to detect a 25% slowing of atrophy (compared to non-carriers) over 12 and 24 months with 80% power and 95% significance. Results:Demographics for trial-eligible participants are shown in the Table and atrophy rates for different regions are in the Figure. The most promising regions were the precuneus (number of subjects per arm sample size [95% confidence interval] at 12 months1⁄4798[486-1458], 24 months1⁄4403[259-702]); ventricles (12 months1⁄4834[473-2105], 24 months1⁄4442[268-894]); posterior cingulate (12 months1⁄41173 [674-2440], 24 months1⁄4469[295-929]); and angular gyrus (12 months1⁄41275[668-3425], 24 months1⁄4678[378-1591]). Conclusions:A number of brain regions, notably posterior cingulate and precuneus, provide power to track change that is comparable to global atrophy measured from ventricles. Feasible sample sizes can be obtained at 24-month follow-up. Further strategies to reduce sample size should include trial enrichment using biomarker status or participants with the same mutation (e.g. presenilin1), improving atrophy measurements with direct measures between timepoints (e.g., boundary shift integral) or combining the most sensitive regions into one summary metric.

Erratum to “Prediction of Treatment Response to Donepezil using Automated Hippocampal Subfields Volumes Segmentation in Patients with Mild Alzheimer's Disease”

[This corrects the article on p. 698 in vol. 14.].